Cardiac overload leads to hypertrophy, but the hypertrophy seen with preload is different from that following afterload, and the response to therapy is also different. The present proposal details studies to pinpoint the difference in protein synthetic response to both forms of stress by tracing the sequence of events following onset of preload such as adenylcyclase activity, nuclear polymerase activity, polysome aggregation and synthesis of proteins in cell free systems as well as ventricular total and contractile proteins. Both afterload and preload stresses will be induced in vitro in a left ventricular model as well as in a right ventricular model with controlled coronary flow. The questions to be answered are 1) Is the translation of mechanical stress of preloading to any altered RNA or protein synthesis qualitatively or quantitatively different from that described in afterload? 2) Which contractile proteins are preferentially synthesized in acute preload compared to afterload? 3) Will protein degradation play a role in preload stress or will there be little change as seen in acute afterload? 4) Will there be preferential synthesis of any protein such as collagen in preload compared to the lack of effect in acute afterload? The second main objective will direct attention to the effects of hypoxia and anoxia on the protein synthetic responses to afterload and preload stresses and the effects of oxygen deprivation on the biochemical sequence leading to any protein synthetic alteration studied. Further, the influence of hypoxia and anoxia on possible preferential synthesis of specific proteins as collagen will be examined in the two hemodynamic stresses. The effects of aging, protein deficiency and ethanol intake will be studied in an attack on the problem of alcoholic cardiomyopathy. Questions to be asked include 1) What will the effect of these latter conditions be on the response of the heart to acute stress of preload and afterload with respect to protein synthesis and degradation? 2) Will the proteins synthesized be the same in the older, protein deficient, or alcoholic animal heart? Thus, the rationale will be to find the abnormal protein synthetic response in the varied stresses so that therapeutic action may be directed toward these alterations.